Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts
Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts
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DOI：
10.1093/eurheartj/ehn167
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发表时间：
2008-06-01
影响因子：
39.3
通讯作者：
Zhao, Shi-Hua
中科院分区：
文献类型：
--
作者：
Yang, Yue-Jin;Qian, Hai-Yan;Zhao, Shi-Hua
目的探讨阿托伐他汀(Ator)能否改善移植于心肌梗死后心肌的骨髓间充质干细胞(MSCs)存活和分化的心脏微环境。方法与结果采用冠状动脉结扎法造成心肌梗死，再灌注后立即将自体骨髓间充质干细胞移植到经Ator或不加Ator预处理的中国猪心脏内。移植后6周，根据SPECT和MRI的评估，所有患有ATOR的动物与未治疗的动物相比，心脏的灌注量和收缩能力都有所改善。在Ator处理的MSC移植动物中，观察到移植的MSCs的存活率和分化程度增加，梗死面积减少。在没有ATOR的情况下，MSC移植在血流灌注和形态上只有轻微的改善。联合应用Ator和MSCs可明显抑制心肌细胞的凋亡，减轻氧化应激，抑制炎性细胞因子的表达。结论Ator通过为移植MSCs的存活和分化创造更好的环境，对急性心肌梗死再灌注心肌具有保护作用。Ator/干细胞联合治疗的益处可能来自他汀类药物介导的抑制心肌梗死后的细胞凋亡、氧化应激和炎症反应。
Aims To investigate whether Atorvastatin (Ator) treatment improves the cardiac micro-environment that facilitates survival and differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) implanted in the post-infarct myocardium.Methods and results Myocardial infarction was created by coronary ligation and immediately after reperfusion, autologous bone-marrow-derived MSCs were transplanted into the hearts of Chinese swine that were pretreated with or without Ator. Six weeks after transplantation, as evaluated by SPECT and MRI all the animals with Ator showed improved cardiac perfusion and contractility when compared with untreated. Increased survival and differentiation of implanted MSCs and decreased infarct area were observed in the Ator-treated, MSC-implanted animals. In the absence of Ator, MSC transplantation only achieved a modest improvement in perfusion and morphology. The combined treatment with Ator and MSCs significantly inhibited cardiac cell apoptosis, reduced oxidative stress, and suppressed expression of the inflammatory cytokines in the post-infarct myocardium.Conclusion Ator treatment may protect the myocardium undergoing acute infarction and reperfusion by creating a better environment for the survival and differentiation of implanted MSCs. The benefit of the Ator/stem cell combined therapy may result from the statin-mediated inhibition of apoptosis, oxidative stress, and inflammation in the infarcted myocardium.